Recent research has established the involvement of the thymus in the functioning of the immune system in mammalian species. It is in the thymus that haemopoietic stem cells become differentiated to mature immunocompetent lymphocytes called T-cells, which circulate to the blood, lymph, spleen and lymph nodes. The T-cells have immunological specificity and are involved in the cell-mediated immune responses, such as graft responses, response to viral infections, response to neoplasms and so forth. The body's response to antigenic material, such as for example in response to bacterial attack, is the province of antibody secreting cells, called B-cells, which are derived from bone marrow stem cells, but which are not differentiated in the thymus. The antibody response to an antigen, in many cases, requires the presence of appropriate T-cells, so that T-cells, and consequently the thymus, are necessary for the body's immune system to make not only cellular immunity responses, but also humoral antibody response. The thymic induction of the necessary differentiation of stem cells to T-cells is mediated by secretions of thymic hormones by the epithelial cells of the thymus.
The great interest in thymic substances, which may be implicated in various aspects of the immune response, has been instrumental in creating a very productive research effort. As a result of this research, a number of thymic substances have been reported in the literature. In an article by Low et al. in The Journal of Biological Chemistry, volume 254, pages 981-993, 1979, there are disclosures regarding the potent immunopotentiating effect of the partially purified extract from thymus tissue termed thymosin Fraction 5. It has been shown that this thymosin fraction corrects some of the deficiencies resulting from lack of thymic function in a number of animal models, as well as in humans with primary immunodeficiency diseases and in immuno-suppressed cancer patients.
Further, in the Low et al. article, there is disclosed thay thymosin Fraction 5 is composed of several polypeptide components, two of which are designated thymosin .alpha..sub.1 and polypeptide .beta..sub.1. Of these two major components, thymosin .alpha..sub.1 has been demonstrated to be a potent immunologically active thymic polypeptide, which is 10-1,000 times as active as the parent thymosin Fraction 5 when assayed in several biological models, including an in vivo mouse mitogen assay, an in vitro lymphokine assay measuring production of macrophage inhibitor factor (MIF), an in vitro induction of Lyt surface markers on putative T-cell precursors, and an in vitro human E-rosette assay measuring the production of T-cells.
The Low et al. article further establishes the sequence of the 28 amino acids comprising thymosin .alpha..sub.1.
The present invention relates to short peptide sequences which have been found to exhibit characteristics of the long chain polypeptide isolated and named thymosin .alpha..sub.1.